Abstract For an eligible patient with end stage kidney disease (ESRD), a living donor (LD) kidney transplant is the best option. But the LD has to have a major operation with surgical risks and the potential long-term risks of living with a single kidney. A number of studies comparing LDs with age, gender and race/ethnicity-matched general population controls have found no differences in long-term outcomes between the LDs and controls. However, recent studies comparing LDs to healthy matched controls have reported that the LDs are at increased risk for ESRD and death. There have been concerns about the matching of LDs and controls in these studies, including the matched controls were not contemporaneous [born in the same year]; were not from the same geographic area; were not known to be healthy on the date that matched the date of donation; and were not matched for family history of ESRD. Each of these factors can impact the risk of developing kidney disease and consequences of kidney disease. There have been concerns about the limited follow-up and the statistical analyses in these studies. In fact, some commentaries have suggested that the LD risk was under-estimated; others, overestimated. Having a complete and accurate understanding of true long-term LD risks is important to provide data to inform future LD candidates (informed consent), as well as to inform the design of long-term health maintenance/surveillance of donors. Government agencies, other stakeholders and LDs themselves are asking for better quality long-term data on LD outcomes. The University of Minnesota (U of Mn) and the Mayo Clinic have longstanding LD transplant programs (1st transplant in 1963) with data collection beginning at the time of the first transplant. In addition, the Rochester Epidemiology Project (REP) in the early 1960s established a linked medical records system that has followed the medical history of residents of Olmsted County and surrounding area (same geographic are as U of Mn and Mayo Clinic). Data from the REP has been used to provide long-term data on healthy populations, and methods are in place to identify healthy matched controls from the REP. We will match LDs with contemporaneous REP controls on age, gender, race/ethnicity and other important characteristics known to affect risk of kidney disease (e.g., BMI, smoking history, blood pressure). We will also match LDs and controls for being healthy (with normal renal function) on the date of donation and on family history of kidney disease. Because of the detailed, long-term (>50 year follow-up) quality data in the LD and REP datasets, we will be able to study and provide the best data to date on: LD risk of ESRD and death; LD risk of the much more common intermediate events that precede ESRD or death (e.g., deterioration of kidney function, cardiovascular disease); impact of known risk factors such as BMI or smoking on the risk of donation; the impact of new onset disease after donation (e.g., diabetes, hypertension) on LD outcomes; and the impact of donation on subsequent pregnancies. We will provide most comprehensive data, to date, to inform prospective LDs about long-term risk, and to inform the follow-up and care of current LDs.